Continuous low amplitude direct current stimulation of the crushed peripheral nerve accelerates the early recovery of choline acetyltransferase but not of acetylcholinesterase activity in fast and slow muscles.

We investigated if continuous 1 µA direct current stimulation of the injured nerve, with the cathode electrode at the distal end of the nerve crush injury (cathode stimulation), accelerated the recovery of choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) activity in transiently denervated extensor digitorum longus (EDL) and soleus (SOL) rat muscles. ChAT is a specific marker of cholinergic nerve terminals and may reflect axon ingrowth, and AChE reflects the re-establishment of neuromuscular junctions and recovery of muscle activity. Compared to sham operated animals, the cathode (CA) stimulated rats had a statistically significant larger ChAT activity in the EDL and SOL muscles on days 12 and 14 after nerve crush (P < 0.01, n = 6). The difference in ChAT activity between the groups decreased thereafter. Regarding recovery of muscle AChE, CA stimulation of the crushed sciatic nerve did not detectably accelerate the normalization of activity and pattern of AChE molecular forms in the EDL and SOL muscles. This means that the early rise in ChAT muscle activity in CA stimulated rats was not followed by an accelerated normalization of the neuromuscular transmission in the same group. It is more likely that the higher ChAT activity observed after cathode stimulation indicates a higher ChAT content in regenerating motor nerve endings, rather than a greater number of motor axons entering the muscles. It seems possible that cathode stimulation increased ChAT axonal transport, causing the early increase of ChAT content in the nerve endings. This raises the possibility that the axon transport and subsequent secretion of a trophic factor(s) from the nerve to the reinnervated muscle are enhanced as well, thus shortening the overall time of muscle force recovery in the absence of an appreciable acceleration of recovery of the neuromuscular transmission.

Muscle force recovery after continuous direct current stimulation of a crushed nerve.

The purpose of this work was to examine whether, after sciatic axonotmesis, continuous low-amplitude direct current stimulation across the nerve crush lesion could affect the overall regeneration rate and shorten the time necessary to restore muscle force. Rats were randomly divided into cathode-stimulated (7 animals with a cathode stimulating electrode at the distal end of the nerve crush), anode-stimulated (6 animals with an anode stimulating electrode at the distal end of the nerve crush) and sham-treated (6 animals) groups. The recovery of muscle force was assessed by measuring the isometric tetanic contraction of the plantar flexor muscles once weekly, for five weeks in all groups. There was no statistically significant difference (P > 0.05) among the three groups from the first to the third week after the nerve crush. The cathode-stimulated animals had a statistically significantly enhanced muscle force recovery in the fourth (P = 0.023) and fifth week (P = 0.003) after the nerve crush, when compared to the anode-stimulated and sham-treated groups. From the first to the fifth week after the nerve crush there was no statistically significant difference (P > 0.05) in muscle force between the anode-stimulated and sham groups. After axonotmesis, the average ratio of normalized muscle force to normalized body weight in the cathode-stimulated group reached the pre-crush control value in the fourth week following the nerve injury. This ratio was significantly lower all five weeks compared to the initial one before axonotmesis in anode-stimulated and sham-treated groups. Placing the cathode-stimulating electrode at the distal end of the nerve crush seems to have shortened the overall time of muscle force recovery. A possible mechanism for the enhancement of muscle force recovery in the cathode-stimulated group is proposed.